DPOAE监测一次性大剂量顺铂致豚鼠耳毒性的实验研究

目的观察一次性大剂量顺铂注射后豚鼠畸变产物耳声发射(DPOAE)和内耳形态学的依时性改变,探讨应用耳声发射监测顺铂耳毒性的最佳时机。方法将豚鼠随机分为对照组(A组)及实验组(B、C、D组),每组6只,A组皮下注射生理盐水,B、C、D各组一次性皮下注射顺铂(10mg/kg),分别于给药前及给药后第3(B组)、5(C组)、10(D组)天检测DPOAE,比较给药前、后DPOAE的幅值的变化,并行耳蜗铺片,观察毛细胞缺失率及耳蜗形态学的改变。结果给药后第3天,DPOAE的幅值仅8kHz处有明显改变(P<0.05);给药后第5、10天DPOAE幅值明显降低(P<0.01)。给药后第3、5、10天,耳蜗外毛细胞缺失率分别为4.34%±3.20%、16.14%±9.15%、18.25%±9.04%。在第5、10天后尚可见血管纹充血以及螺旋神经节细胞肿胀缺失。结论顺铂的耳毒性主要作用于耳蜗底回、中回的外毛细胞,用药后第3~5天应用畸变产物耳声发射检查能早期发现其耳毒性损伤。

The Application of DPOAE to Monitor the Ototoxicity of Guinea Pig Injected with Large dosage of Cis-Platinum

Objective To investigate the application of the DPOAE for monitoring the ototoxicity of gainea pig injected with large dosage of cis-platinum and to observe the changes in otoacoustic emissions and the morphology of cochlea.Methods The animals were randomly divided into four group.Each animal received cis-platinum(10 mg/kg subcutaneously) or an equivalent volume of normal saline subcutaneously. DPOAE was measured before and 3,5,10 days after drug or saline administration. The cochlea was removed and processed for histological examination.Results The DPOAE results showed a marked transition from little ototoxic effect to noticeable effect between the 3 day and the 5 day. 3, 5,10 day after administration cisplatinum the histological results corresponded well with the DPOAE results.Conclusion Acute cis-platinum administration results in degeneration of the organ of Corti with partial or complete loss of outer hair cells(OHCs).In addition to the toxic effects of cis-platinum upon the organ of Corti, it also has impact on the stria vascularis. It seems reasonable that DPOAE may be a useful clinical tool for monitoring ototoxic effects of drugs.